Research Paper Volume 12, Issue 15 pp 15756—15770
MiR-483 induces senescence of human adipose-derived mesenchymal stem cells through IGF1 inhibition
- 1 Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
Received: October 18, 2019 Accepted: July 6, 2020 Published: August 15, 2020
https://doi.org/10.18632/aging.103818How to Cite
Copyright © 2020 Shen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Human adipose-derived mesenchymal stem cells (hADSCs) are an ideal source of seed cells for regenerative applications and tissue engineering. However, long-term in vitro culture of hADSCs reduces their quantity and quality, which lessens their value in research and clinical applications. The molecular mechanisms underlying this biological process are poorly defined. Recently identified microRNAs (miRNAs) have emerged as critical modulators of cellular senescence. In this study, we examined the changes in hADSCs undergoing senescence. Significant miR-483-3p upregulation was noted during in vitro passaging of hADSCs, which correlated with the adipogenic differentiation and cellular senescence. Knockdown of miR-483-3p retarded the adipogenic differentiation potential of hADSCs and reduced cellular senescence. Dual-luciferase reporter assays identified insulin-like growth factor-1 (IGF1) as the target gene of miR-483-3p. IGF1 inhibition confirmed its inhibitory effects on replicative senescence in hADSCs. In conclusion, our study revealed essential regulatory roles of miR-483-3p in the adipogenesis and aging of hADSCs mediated by targeting IGF1.
Abbreviations
hADSCs: Human adipose-derived mesenchymal stem cells; miRNAs: microRNAs; SA-β-gal: senescence-associated β-galactosidase; IGF1: insulin-like growth factor-1; MSCs: Mesenchymal stem cells; mRNAs: messenger RNAs; IGF2: insulin-like growth factor-2; 3′ UTR: 3′ untranslated region; CCK-8: Cell counting kit-8; RT-qPCR: real-time quantitative PCR; LPL: lipoprotein lipase; PPARγ: peroxisome proliferator-activated receptor gamma; OGT: O-linked N-acetylglucosamine transferase; CLCN3: chloride voltage-gated channel; siRNA: small interfering RNA; TERT: telomerase reverse transcriptase.